Virologic Efficacy of Casirivimab and Imdevimab COVID-19 Antibody Combination in Outpatients With SARS-CoV-2 Infection
Authors: Cynthia Portal-Celhay, Eduardo Forleo-Neto, Will Eagan, Bret J. Musser, John D. Davis, Kenneth C. Turner, Thomas Norton, Andrea T. Hooper, Jennifer D. Hamilton, Cynthia Pan, Adnan Mahmood, Alina Baum, Christos A. Kyratsous, Yunji Kim, Janie Parrino, Wendy Kampman, Lilia Roque-Guerrero, Roxana Stoici, Adil Fatakia, Yuhwen Soo, Gregory P. Geba, Bari Kowal, A. Thomas DiCioccio, Neil Stahl, Leah Lipsich, Ned Braunstein, Gary A. Herman, George D. Yancopoulos, David M. Weinreich, Dario Altamirano, Dickson Ellington, Najmuddin Karimjee, Munib Daudjee, Jessica Laabs, Karen Marler, Natalee Calais, Zachary Sheppard, Kristy Carroll, Anita Kohli, Vicki McIntyre, Yessica Sachdeva, Ashley Carney, Amanda McFarland, Dina Gibson, Victorine Ekoko, Kenneth Kim, Jason Ahn, Nayna Paryani, Amber Mottola, Eva Day, Martha Navarro, Apinya Vutikullird, Lilia Roque-Guerrero, Ana Gomez Ramirez, Javier Capote, Gisel Paz, Nancy Patel, Ravikumar Patel, Ryan Sattar, Michael Seep, Celeste Brown, Joshua Whatley, Dennis Levinson, Azazuddin Ahmed, Norman James, Saad Alvi, Ann Kuehl, Robinson Koilpillai, Stephanie Cassady, Jennifer Cox, Eduardo Torres, Michael Winnie, Omesh Verma, Richard Leggett, Ramon Reyes, Keith Beck, Brian Poliquin, Murtaza Mussaji, Jignesh Shah, John Eppensteiner, Alexander Limkakeng, Samuel Francis, Haresh Boghara, Sunny Patel, Bari Eichelbaum, Duane Anderson, Sean Su, Alexander Akhavan, Joy Venglik, Diana Kirby, Crista Fedora, Faisal A. Fakih, Faisal M. Fakih, Fernando Alvarado, Daniel Layish, Jose Diaz, Andres Perez, Bhaktasharan Patel, Gary Tarshis, Roxana Stoici, Gualberto Perez, Joseph Pica, Enrique Villareal, Farbod Raiszadeh, Sharon Mannheimer, Khaing T. Myint, Lovelyamma Varghese, Anya T. Weerasinghe, Raji Ayinla, Hussein Assallum, Akari Kyaw, Simona Bratu, Robin O'Reilly, Donna Dowie, Karina Chan, Suraj Saggar, Thomas Birch, Benjamin De La Rosa, Karyna Neyra, Erina Kunwar, Hessam Aazami, Cheryl Bland, Mary Michelle Nolasco, Howard Huang, Jihad Georges Youssef, Simon Yau, Ahmad Goodarzi, Mukhtar Al-Saadi, Faisal Zahiruddin, Jeffrey Kingsley, April Pixler, Christopher deFilippi, Christopher King, Lindsay Clevenger, Richard Wilkerson, Shivakumar Narayanan, Joel Chua, Jennifer Husson, John Baddley, Rajasekaran Annamalai, Huy Nguyen, Nizar Nayani, Mahalakshmi Ramchandra, Thomas Herchline, Steve Burdette, Godson Oguchi, Judepatricks Onyema, Moti Ramgopal, Brenda Jacobs, Terence Chang, Robbyn Traylor, Lenee Gordon, John McDivitt, Lizette Castro, Lawrence Sher, Monica Saad, LeighAnn Schmidt, David Brabham, Tarek Naguib, Mark Sigler, Jennifer Killion, Rupal Amin, Timothy Lowry, Kevin Cannon, Mesha Chadwick, Trevan Fischer, Terese Hammond, Anmol Rangoola, Oscar Galvez, Fausto Castillo, Edward Cordasco, Brian Zeno, Heather Lee, Peter Ruane, Peter Wolfe, Kenny Trinidad, Isaac Berlin, Mark Savant, Edna Yee, Alan Skolnick, Harold Minkowitz, David Leiman, Upinder Singh, Yvonne Maldonado, Jason Andrews, Chaitan Khosla, Hector Bonilla, Esteban Olivera, Mayra Abreu, Adil Fatakia, Marissa Miller, Kristen Clinton, Gary Reiss, Olayemi Osiyemi, Jose A. Menajovsky-Chaves, Christina Campbell, Stephanie Martinez, Gerard Acloque, Agustin Martinez, Kami Kim, Seetha Lakshmi, Asa Oxner, Jason Wilson, Lucy Guerra, Tiffany Vasey, Susannah Hall, Joseph Bocchini, Clint Wilson, Kathryn Adams, Dawn Applegate, Dhanalakshmi Barron, Mary Basilious, Travis Bernardo, Eleonora Bianchi, Dona Bianco, Manika Bista, Mandi Blackmon, Teresa Blake, Jessica Boarder, Lisa Boersma, Denise Bonhomme, Peter Boutros, Derrick Bramble, Aurora Breazna, Alison Brown, Elizabeth Bucknam, Tyrah Chatman, Ravikanth Chava, Donna Cohen, Nikki Covino, S. Balachandra Dass, Amy Davis, Jeanelle De Villiers, Sherrie DeGuzman, Monica DeYoung, Marc Dickens, Lacey Douthat, Ajla Dupljak, Joseph Fitzgerald, Kyle Foster, Samit Ganguly, Paul Gao, Peter Gasparini, Evelyn Gasparino, Heath Gonzalez, Ruchin Gorawala, Daya Gulabani, Mary Hasinsky, Sheree Hairston, Robert Hamlin, Dawlat Hassan, Russell Haywood, Brian Head, Philippa Hearld, Ingeborg Heirman, Olga Herrera, Romana Hosain, Susan Irvin, Ramya Iyer, Lisa Jackson, Rohit Kamath, Helen Kang, Denise Kennedy, Elisa King, Michael Klingler, Mi Young Kwon, Carol Lee, Maria Lichtschein, David Liu, Kristy Macci, Marco Mancini, Nagaratna Reddy Medapti, Nilang Mehta, Colin McDonald, Kristina McGuire, Stephanie Miller, Nkechi Moghalu, Kosalai Mohan, Nicholas Moore, Emily Nanna, Soraya Nossoughi, Esther Huffman O'Keefe, Carrie Papazian, Michael Partridge, Christina Perry, Cynthia Plante, Kalpana Pullakhandam, Emina Radoncic, John Rembis, Nelson Rita, Mivianisse Rodriguez, Neena Sarkar, Viral Seth, Ileana Schirmer, Liyang Shao, Shelley Geila Shapiro, Matthew Silverman, Carmella Simiele, Isarael Simonetti, Lisa Sherpinsky, Anne Smith, Jasmine Smith, Pamela Snodgrass, Michel Tarabocchia, Karen Thabet, Yanmei Tian, Caryn Trbovic, Ngan Trinh, Violet Vincent, Jeff Watts, Jianguo (Victor) Wei, Collen Whetzel, Joseph Wolken, Karen Yau, Ori Yellin, Jeannie Yo, Yuming Zhao, Bryan Zhu
Journal: JAMA Network Open (2022)

<h3>Importance</h3> The monoclonal antibody combination of casirivimab and imdevimab reduced viral load, hospitalization, or death when administered as a 1200-mg or greater intravenous (IV) dose in a phase 3 COVID-19 outpatient study. Subcutaneous (SC) and/or lower IV doses should increase accessibility and/or drug supplies for patients. <h3>Objective</h3> To assess the virologic efficacy of casirivimab and imdevimab across different IV and SC doses compared with placebo. <h3>Design, Setting, and Participants</h3> This phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study included outpatients with SARS-CoV-2 infection at 47 sites across the United States. Participants could be symptomatic or asymptomatic; symptomatic patients with risk factors for severe COVID-19 were excluded. Data were collected from December 15, 2020, to March 4, 2021. <h3>Interventions</h3> Patients were randomized to a single IV dose (523 patients) of casirivimab and imdevimab at 300, 600, 1200, or 2400 mg or placebo; or a single SC dose (292 patients) of casirivimab and imdevimab at 600 or 1200 mg or placebo. <h3>Main Outcomes and Measures</h3> The primary end point was the time-weighted average daily change from baseline (TWACB) in viral load from day 1 (baseline) through day 7 in patients seronegative for SARS-CoV-2 at baseline. <h3>Results</h3> Among 815 randomized participants, 507 (282 randomized to IV treatment, 148 randomized to SC treatment, and 77 randomized to placebo) were seronegative at baseline and included in the primary efficacy analysis. Participants randomized to IV had a mean (SD) age of 34.6 (9.6) years (160 [44.6%] men; 14 [3.9%] Black; 121 [33.7%] Hispanic or Latino; 309 [86.1%] White); those randomized to SC had a mean age of 34.1 (10.0) years (102 [45.3%] men; 75 [34.7%] Hispanic or Latino; 6 [2.7%] Black; 190 [84.4%] White). All casirivimab and imdevimab treatments showed significant virologic reduction through day 7. Least-squares mean differences in TWACB viral load for casirivimab and imdevimab vs placebo ranged from –0.56 (95% CI; –0.89 to –0.24) log<sub>10</sub>copies/mL for the 1200-mg IV dose to –0.71 (95% CI, –1.05 to –0.38) log<sub>10</sub>copies/mL for the 2400-mg IV dose. There were no adverse safety signals or dose-related safety findings, grade 2 or greater infusion-related or hypersensitivity reactions, grade 3 or greater injection-site reactions, or fatalities. Two serious adverse events not related to COVID-19 or the study drug were reported. <h3>Conclusions and Relevance</h3> In this randomized clinical trial including outpatients with asymptomatic and low-risk symptomatic SARS-CoV-2, all IV and SC doses of casirivimab and imdevimab comparably reduced viral load. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT04666441